Ghrelin and Beta Cell Function in Diabetes

NCT02440061 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: Pro00060865R01DK097550
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Ghrelin is a hormone naturally produced in the stomach and the gut. The purpose of this research study is to determine the role of this gut hormone in the regulation of insulin secretion from the pancreas and glucose disposal after we eat. The investigators hypothesize that ghrelin has an effect on the pancreas and on how our body handles glucose after we eat. The investigators will compare insulin secretion and glucose changes during meal ingestion while either acyl ghrelin (AG) or saline (salt solution) is being infused through your vein on separate study days. AG is a form of the ghrelin hormone that has a small modification to it that allows it to bind to a specific receptor. The investigators hypothesize that AG has an effect on how the body handles glucose after a meal. AG has been approved by the U.S. Food and Drug Administration (FDA) for human research only. This study will also involve the use of a medicine called arginine, which is a naturally occurring product and found in many nutritional supplements. Its use in this study is investigational. The use of arginine helps maximize insulin release from the pancreas so the investigators can better examine whether AG affects insulin secretion.

Conditions

Type 2 Diabetes Mellitus

Keywords

Ghrelin; age, BMI, and gender matched controls

Outcome Measures

Primary Outcomes (4)

• Postprandial insulin secretion (ISR-meal)

  Postprandial insulin secretion (ISR-meal) will be derived from plasma C-peptide concentrations during MTT (0-240 min) using deconvolution with population estimates of C-peptide clearance.

  approximately 8 weeks

• Index of β-cell sensitivity to glucose

  Index of β-cell sensitivity to glucose will be calculated as incremental insulin/glucose (I/G) AUC (ΔAUCI/G).

  approximately 8 weeks

• Whole body insulin sensitivity using the Matsuda Index

  The Matsuda Index is a well-known index of insulin sensitivity derived from several glucose and insulin values obtained during a mixed meal

  approximately 8 weeks

• β-cell function (DI-meal)

  β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index

  approximately 8 weeks

Study Arms (2)

Study Group: Type 2 Diabetes Mellitus (T2DM)

ACTIVE COMPARATOR

Subjects with Type 2 Diabetes Mellitus (T2DM). Subjects will receive AG and saline infusions, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.

Drug: Synthetic human AG; Drug: Arginine; Drug: 0.9% saline solution

Control Group

ACTIVE COMPARATOR

Control group of healthy subjects. Subjects will receive AG and saline, but the order of which they receive will be random and they will not be told which one they are receiving on each given visit. Arginine will be used at both study visits.

Drug: Synthetic human AG; Drug: Arginine; Drug: 0.9% saline solution

Interventions

Synthetic human AG DRUG

Synthetic human AG (0.28 μg/kg) bolus over 1 minute followed by 2 μg/kg/hr continuous infusion for 4.5 hours.

Control Group; Study Group: Type 2 Diabetes Mellitus (T2DM)

Arginine DRUG

Arginine hydrochloride (5 g) intravenously over 45 seconds.

Control Group; Study Group: Type 2 Diabetes Mellitus (T2DM)

0.9% saline solution DRUG

A continuous infusion of 0.9% saline solution (control) for 4.5 hours.

Control Group; Study Group: Type 2 Diabetes Mellitus (T2DM)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Established T2DM with good to moderate glycemic control
• HbA1c \< 8.5%
• Diabetes treatment with metformin, sulfonylurea, thiazolidinediones or combination of these medications; with no use of insulin during the study period
• BMI ≤ 45.0 kg/m2
• HbA1c ≤ 5.7%
• Fasting plasma glucose ≤ 95 mg/dL
• BMI ≤ 45.0 kg/m2

You may not qualify if:

• All subjects will be excluded for the following reasons:
• History of myocardial infarction or arrhythmia within the past year, abnormal electrocardiogram (ECG) with evidence of ischemia or arrhythmia, history or symptoms of congestive heart failure
• Uncontrolled hypertension
• History or active liver or renal disease (AST or ALT \>2x upper limits of normal, calculated glomerular filtration rate \[eGFR\] \<60 at screening)
• History of pituitary or adrenal disorders or neuroendocrine tumor
• Anemia defined as hematocrit \<33% at screening
• Active cancer diagnosis or currently undergoing cancer treatment
• History of anorexia nervosa or previous gastrointestinal tract surgery
• Pregnancy or lactation
• Control subjects will be excluded for the following reasons:
• History or clinical evidence of impaired fasting glucose or impaired glucose tolerance on a 75 g OGTT, established diabetes mellitus, or taking medications prescribed for diabetes
• Use of medications that alter insulin sensitivity (i.e. niacin, glucocorticoids, metformin)

Sponsors & Collaborators

• Jenny Tong, MD, MPH: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Duke Center For Living

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Arginine; Saline Solution

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jenny Tong, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 12, 2015
• Study Start: May 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: April 2, 2018

Record last verified: 2018-03

Locations

US (1)